Ethodolic acid, chemically definable as 1,8-diethyl-1,3,4,9-tetrahydropyran [3,4-b]indole-1-acetic acid, has the following structural formula: ##STR1## and is known and therapeutically used as an anti-inflammatory non steroidal active principle.
It has an asymmetrical centre and exists therefore as a mixture of two enantiomers. In the first report on the resolution of the two enantiomers (C. A. Demerson and al., J. Med. Chem., 26,1778, (1983)) the pharmacological activity is reported as almost totally due to the dextrorotatory isomer.
The absolute configuration of the (+) enantiomer has been subsequently determined and defined as S in accordance to the Cahn-Ingold-Prelog convention (C. A. Demerson, J. Med. Chem., 29,871,(1986)).
Various methodologies have been proposed in the course of years so as to carry out such resolution and, hence, the isolation of the pharmacologically active dextrorotatory isomer.
Canadian Patent No. 190230 to American Home Products Corp. discloses a resolution method which comprises the esterification of the racemic mixture of the two enantiomers with (-)-borneol and the further chromatographic separation in a silica column of the two diastereoisomers, from the hydrolysis of which the respective ethodolic acid enantiomers are obtained.
Regarding more specifically the dextrorotatory S isomer to be obtained, U.S. Pat. No. 4,501,899 entails the use of cholesterilaniline for the optical resolution.
In U.S. Pat. No. 4,515,961 the enrichment of an enantiomer by selective precipitation is described, triggered by the presence of an excess of enantiomer added to the crystallization mixture.
U.S. Pat. No. 4,520,203 teaches the resolution being accomplished by cinconine, whereas U.S. Pat. No. 4,544,757 describes still the (-)-borneal as the esterification agent.
The methods known until now show various drawbacks especially so far the yields are concerned, thus bringing about industrial problems.